In HNF4A-MODY and HNF1A-MODY patients, normal or even increased insulin sensitivity together with glucose-independent mechanism of action of the first-line therapy - sulphonylurea derivatives - often leads to hypoglycemia, even at the much lower dose used in type 2 diabetes.
We hypothesized that common variants at the <i>HNF1A</i> locus (rs1169288 [rs1169288" genes_norm="6927">I27L], rs1800574 [rs1800574" genes_norm="6927">A98V]), which are associated with type 2 diabetes susceptibility, may modify age at diabetes diagnosis in individuals with HNF1A-MODY.
This study aimed to investigate differences in serum miR-122 levels in Chinese patients with different forms of diabetes, including T2DM, type 1 diabetes (T1DM), HNF1A variant-induced diabetes (HNF1A-DM), glucokinase variant-induced diabetes (GCK-DM), and mitochondrial A3243G mutation-induced diabetes (MDM).
This study demonstrated that the common HNF1A diplotype of three risk variants may be an independent risk factor for the development of DR resulting from poor glycemic control in normal-weight patients with T2DM.
Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231).
MODY3 experienced a larger decrease in the ratio of NEFA to insulin (NEFA 30-0 / insulin 30-0: -39 [-78; -30] x104) in the early post-prandial period (0-30 minutes) compared to controls and to T2D (-2.0 [-0.6; -6.4] x104; P<0.05).
Tcf7 (in mice) or TCF7 (in humans) levels are lower in islets taken from diabetic mice and in humans with type 2 diabetes; knockdown of TCF7 in human and mouse islets impairs the cytoprotective responsiveness to GIP and enhances the magnitude of apoptotic injury, whereas restoring TCF1 levels in beta cells from Gipr(-/-βCell) mice lowers the number of apoptotic cells compared to that seen in MIP-Cre controls.